Since the publication of the 2013 cholesterol guideline, the U.S. Food and Drug Administration has approved proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors for certain patients and the recent publication of the HPS2-THRIVE and IMPROVE-IT trials have provided new evidence about adding non-statin therapies to statins as combination therapy. The writing committee supports consideration of adding ezetimibe 10 mg daily as the first non-statin agent for many higher-risk patient groups. However, they do not recommend niacin as an additional non-statin therapy for the situations discussed in the document. Consistent with the 2013 guideline, this new document recommends looking first at lifestyle issues, including diet, exercise and smoking, followed by statin therapy.

The algorithms in the document provide a suggested clinical workflow for consideration of the addition of non-statin therapies to evidence-based statin therapy, and assume that patients are in one of the four evidence-based statin benefit groups identified in the 2013 guideline. The writing committee explains that for other groups of patients, care should be individualized.

Defining thresholds of low-density lipoprotein cholesterol (LDL-C), in terms of percentage reduction and absolute values, for consideration of net atherosclerotic cardiovascular disease (ASCVD) risk-reduction benefit, is critical to helping determine use of additional non-statin therapies in selected high-risk patients. The writing committee emphasizes that these are not firm triggers for adding medication but factors that may be considered within the broader context of an individual patient’s clinical situation.

Additional considerations for the initiation of non-statin therapies include the extent of available scientific evidence for safety and tolerability, potential for drug-drug interactions, efficacy of additional LDL-C lowering in ASCVD event reduction, cost, convenience and medication storage, pill burden, route of administration, potential to jeopardize adherence to evidence-based therapies, and importantly, patient preferences, according to the document.

“This consensus pathway document is the first in a new format, where we offer guidance to clinicians in an easy to understand algorithm approach framed in a data supported fashion,” said James L. Januzzi Jr., MD, FACC, chair of the ACC’s Task Force on Clinical Expert Consensus Documents. “While like any consensus document before it, this effort contains abundant useful information, the ACC recognizes the importance of providing useful decision support to busy clinicians as well. I feel the authors threaded the needle perfectly with this pathway, providing a useful resource for understanding the appropriate use of non-statin therapies while simultaneously guiding clinicians for such use.”